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Safety and Efficacy Study of Torisel and Liposomal Doxorubicin for Patients With Recurrent Sarcoma

8 mars 2019 uppdaterad av: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phase I/II Trial of Torisel and Liposomal Doxorubicin in Patients With Advanced Soft Tissue and Bone Sarcomas

The purpose of this study is to identify a safe dosing regimen for the combination of Torisel and liposomal doxorubicin in patients with recurrent sarcoma. A secondary purpose of the study is to determine how effective this combination is for the treatment of recurrent sarcoma.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

The effectiveness of treatments for recurrent sarcomas is quite limited. One hypothesis to explain the refractory nature of recurrent sarcomas is the existence of chemotherapy-resistant sarcoma stem cells.

Studietyp

Interventionell

Inskrivning (Faktisk)

24

Fas

  • Fas 2
  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Förenta staterna
    • Maryland
      • Baltimore, Maryland, Förenta staterna, 21231
        • Johns Hopkins University

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

1 år och äldre (Barn, Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  • Histologically confirmed sarcoma that is recurrent or refractory to conventional treatment
  • Measurable disease by RECIST criteria
  • ECOG (Eastern Cooperative Oncology Group) performance status < 2 (or Lansky/Karnofsky > 60% for children)
  • Life expectancy greater than 3 months
  • Adequate organ function
  • absolute neutrophil count at least 1,500
  • platelets at least 100,000
  • bilirubin less than 1.5 x upper limit of normal
  • AST (aspartate aminotransferase) and ALT(alanine aminotransferase) less than 2.5 x upper limit of normal
  • creatinine less than 1.5 x upper limit of normal OR creatinine clearance at least 60 ml/min/1.73 m2
  • fasting serum cholesterol less than 350
  • fasting serum triglycerides less than 400
  • PT (prothrombin) or INR (international normalized ratio) less than 1.3 x upper limit of normal
  • normal urinalysis
  • Ability to understand and sign the informed consent document

Exclusion Criteria:

  • Prior chemotherapy or radiotherapy within 3 weeks of entering the study (6 weeks for nitrosoureas or mitomycin C)
  • Prior treatment with a tyrosine kinase inhibitor within 10 days of entering the study
  • History of pulmonary hypertension or pneumonitis
  • Patients may not be receiving other investigational agents
  • Prior therapy with rapamycin, rapamycin analogues, or tacrolimus
  • Uncontrolled brain metastases
  • History of grade 3 or 4 hypersensitivity to macrolide antibiotics
  • Concurrent treatment with immunosuppressive agents other than a stable (for more than 2 weeks) dose of corticosteroids
  • Uncontrolled intercurrent illness
  • Pregnancy or breast feeding
  • HIV-positive patients on combination antiretroviral therapy
  • Grade 3 or 4 proteinuria

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: temsirolimus plus liposomal doxorubicin
Single arm study: Dose escalation of temsirolimus plus constant dose of liposomal doxorubicin.
Läkemedel: temsirolimus plus liposomal doxorubicin
Patients were treated with temsirolimus (Torisel) weekly by IV and with liposomal doxorubicin (Doxil) (standard dose) by IV once every 28 days. Cohorts of patients receive sequentially increasing dose of temsirolimus until dose limiting toxicity (DLT) occurred and the maximally tolerated dose (MTD) was identified. The MTD dose was the standard dose of temsirolimus used for the remainder of the study. Dose modifications were based on protocol parameters for toxicities.
Andra namn:
  • Doxil
  • Torisel

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Part 1: Incidence of Dose Limiting Toxicities
Tidsram: End of second 28-day cycle
Dose limiting toxicities in each dose cohort.
End of second 28-day cycle
Part 2: Median Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Tidsram: up to 5 years
Number of days from day 1 of treatment until date of death from any cause.
up to 5 years

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Median Progression-free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Tidsram: up to 3 years
Interval from Date of start of treatment to date of disease progression or death from any cause. Disease progression is defined as at least 20% increase in sum of longest diameter of target lesions or appearance of any new lesions. Subjective determination of significant worsening of disease-related symptoms was considered clinical disease progression.
up to 3 years
Objective Response Rate
Tidsram: up to 5 years
Number of participants who completed at least 2 treatment cycles with evidence of response. Response is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression
up to 5 years
Maximum Observed Plasma Concentration (Cmax)
Tidsram: Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS
Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
Area Under the Curve (AUC)
Tidsram: Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
AUC was calculated using a single compartment model.
Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
Drug Clearance
Tidsram: Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS.
Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
Mean Progression Free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Tidsram: up to 3 years
Interval from start of treatment to disease progression or death from any cause. Disease progression is defined as at least 20% increase in sum of longest diameter of target lesions or appearance of any new lesions. Subjective determination of significant worsening of disease-related symptoms was considered clinical disease progression
up to 3 years
Mean Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Tidsram: up to 5 years
up to 5 years
Time to Response
Tidsram: up to 5 years
Number of days after 2 cycles of treatment, until maximal response is observed.
up to 5 years
Duration of Response
Tidsram: up to 5 years
Number of days until documentation of disease progression or date of death from other cause
up to 5 years
Clinical Benefit Rate
Tidsram: up to 5 years
Number of days from documented improvement to disease progression.
up to 5 years

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Samarbetspartners

Wyeth is now a wholly owned subsidiary of Pfizer
National Comprehensive Cancer Network

Utredare

  • Huvudutredare: David M Loeb, MD, PhD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 september 2009

Primärt slutförande (Faktisk)

1 september 2012

Avslutad studie (Faktisk)

1 september 2012

Studieregistreringsdatum

Först inskickad

28 juli 2009

Först inskickad som uppfyllde QC-kriterierna

29 juli 2009

Första postat (Uppskatta)

30 juli 2009

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

11 mars 2019

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

8 mars 2019

Senast verifierad

1 mars 2019

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • J0963
  • NA_00028490 (Annan identifierare: JHMI-IRB)

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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